Interactions among cells of the blood vessel wall, blood cells, and materials probably contribute to certain reactive processes that limit the long-term success of a number of contemporary cardiovascular therapeutic interventions. For example, such interactions contribute to anastomotic hyperplasia following insertion of small caliber vascular prostheses and hyperplasia following insertion of intravascular stents. Blood-tissue interactions also probably contribute to restenosis following balloon or other types of angioplasty, saphenous vein bypass grafting, and the accelerated arteriosclerosis that complicates solid organ transplantation. Despite the diverse nature of the inciting interventions, common pathobiological mechanism may contribute to these tissue reactions. Signals arising from interactions between biomaterials and soluble or formed blood elements can modulate the functions of the cells that comprise the blood vessel wall. In many instances, altered endothelial function may play a primary or contributory role in vascular lesion formation. Migration and inappropriate proliferation of smooth muscle cells also commonly occur during reactions of blood vessels to interventional therapies. Increased accumulation of extracellular matrix materials and, sometimes, remodeling of this matrix often accompany smooth muscle migration and proliferation and participate in the formation of these vascular lesions. Such altered functions of vascular walls and their interactions with blood elements, including the coagulation system, platelets, and leukocytes, contribute to both initiation and progression of vascular lesions produced by cardiovascular interventions. Late in the natural history of these lesions, complications may arise that can yield significant clinical manifestations. Such complications include fissuring, rupture, ulceration, thrombosis and embolism, calcification of lesions and prosthetic devices, microvascular hemorrhage, and aneurysmal dilatation of vessels. These late complications often involve altered vascular cell functions related to interaction with soluble or formed elements of the blood and, when present, implanted biomaterials.